Human cytomegalovirus (HCMV) is the most important pathogen that limits the success of allogeneic BMT. The infection is associated with an often fatal pneumonitis (IP) particularly in the setting of acute GVHD. The pathophysiology of HCMV associated pneumonitis is not fully understood. This project is designed to answer questions in four areas to extend our understanding of the pathogenesis of this important complication of BMT. Experiments will be performed to determine if HCMV can induce antigenic alterations on cells that make them an enhanced target for subsequent immunologic injury. Experiments have been performed that suggest that HCMV antigen can induce surface antigen changes on lymphocytes, possibly related to enhanced expression of class II antigens. These studies will be extended from this model system to cell lines in order to explore the mechanisms for this HCMV related alteration. The immunologic response of the lung to HCMV will be examined by studying the mononuclear cells obtained by broncho-alveolar lavage in patients who had received allogeneic BMT grafts. These studies (cell surface markers, MHC antigen expression, cytotoxicity) will be correlated with the virologic data from the specimen and the clinical outcome. This will give new information concerning the development of interstitial pneumonia associated with HCMV. Previous work in a GVHD-CMV model analogous to human IP supports the hypothesis that the pathophysiology of murine CMV pneumonitis is immunologically mediated. Studies will be performed to examine the effect of MCMV-infection on the expression of class I and class II MHC antigens on pulmonary tissue and to determine the effect of passive transfer of monoclonal antibodies to class I and class II MHC antigens on MCMV infection, GVHD, and pneumonitis. The administration of murine monoclonal antibody to humans is limited due to host immune responses to species specific antigens. This project will also attempt to convert a murine anti-DR antibody with striking affinity for human class II antigens into a human/murine hybrid antibody. Exon switching technology will be utilized and the recombinant antibody will be compared in activity to the original murine antibody. This converted antibody may be more therapeutically useful in patients with immunologically mediated disorders.